New Aspects of Mitochondrial Uncoupling Proteins (UCPs) and Their Roles in Tumorigenesis
Abstract
:1. Introduction
2. UCPs and Non-Cancer Diseases
3. UCP and Cancer
4. Regulation of UCP in Cancer Cells
5. UCP2 and p53 Signaling
6. Conclusions
References
- Brand, MD. The proton leak across the mitochondrial innermembrane. Biochim. Biophys. Acta 1990, 1018, 128–133. [Google Scholar]
- Brand, MD; Chien, LF; Ainscow, EK; Rolfe, DFS; Porter, RK. The causes and functions of mitochondrial proton leak. Biochim. Biophys. Acta 1994, 1187, 132–139. [Google Scholar]
- Brown, GC; Brand, MD. On the nature of the mitochondrial proton leak. Biochim. Biophys. Acta 1991, 1059, 55–62. [Google Scholar]
- Brand, MD; Brindle, KM; Buckingham, JA; Harper, JA; Rolfe, DFS; Stuart, JA. The significance and mechanism of mitochondrial proton conductance. Int. J. Obes. Relat. Metab. Disord 1999, 23, S4–S11. [Google Scholar]
- Porter, RK; Brand, MD. Causes of differences in respiration rate of hepatocytes from mammals of different body mass. Am. J. Physiol 1995, 269, R1213–R1224. [Google Scholar]
- Rolfe, DFS; Newman, JMB; Buckingham, JA; Clark, MG; Brand, MD. Contribution of mitochondrial proton leak to respiration rate in working skeletal muscle and liver and to SMR. Am. J. Physiol 1999, 276, C692–C699. [Google Scholar]
- Bouillaud, F; Ricquier, D; Thibault, J; Weissenbach, J. Molecular approach to thermogenesis in brown adipose tissue: cDNA cloning of the mitochondrial uncoupling protein. Proc. Natl. Acad. Sci. USA 1985, 82, 445–448. [Google Scholar]
- Fleury, C; Neverova, M; Collins, S; Raimbault, S; Champigny, O; Levi-Meyrueis, C; Bouillard, F; Seldin, MF; Surwit, RS; Ricquier, D; et al. Uncoupling protein-2: A novel gene linked to obesity and hyperinsulinemia. Nat. Genet 1997, 15, 269–272. [Google Scholar]
- Boss, O; Samec, S; Paoloni-Giacobino, A; Rossier, C; Dulloo, A; Seydoux, J; Muzzin, P; Giacobino, JP. Uncoupling protein-3: A new member of the mitochondrial carrier family with tissue-specific expression. FEBS Lett 1997, 408, 39–42. [Google Scholar]
- Mao, W; Yu, XX; Zhong, A; Li, W; Brush, J; Sherwood, SW; Adams, SH; Pan, G. UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells. FEBS Lett 1999, 443, 326–330. [Google Scholar]
- Sanchis, D; Fleury, C; Chomiki, N; Goubern, M; Huang, Q; Neverova, M; Gregoire, F; Easlick, J; Raimbault, S; Levi-Meyrueis, C; et al. BMCP1, a novel mitochondrial carrier with high expression in the central nervous system of humans and rodents, and respiration uncoupling activity in recombinant yeast. J. Biol. Chem 1998, 273, 34611–34615. [Google Scholar]
- Goglia, F; Skulachev, VP. A function for novel uncoupling proteins: antioxidant defense of mitochondrial matrix by translocating fatty acid peroxides from the inner to the outer membrane leaflet. FASEB J 2003, 17, 1585–1591. [Google Scholar]
- Mattson, MP; Kroemer, G. Mitochondria in cell death: novel targets for neuroprotection and cardioprotection. Trends Mol. Med 2003, 9, 196–205. [Google Scholar]
- Mattson, MP; Liu, D. Mitochondrial potassium channels and uncoupling proteins in synaptic plasticity and neuronal cell death. Biochem. Biophys. Res. Commun 2003, 304, 539–549. [Google Scholar]
- Park, JW; Jeong, G; Kim, SJ; Kim, MK; Park, SM. Predictors reflecting the pathological severity of non-alcoholic fatty liver disease: Comprehensive study of clinical and immunohistochemical findings in younger Asian patients. J. Gastroenterol. Hepatol 2007, 4, 491–497. [Google Scholar]
- Day, CP; James, OF. Steatohepatitis: a tale of two “hits”? Gastroenterology 1998, 114, 842–845. [Google Scholar]
- Cortez-Pinto, H; Chatham, J; Chacko, VP; Arnold, C; Rashid, A; Diehl, AM. Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study. JAMA 1999, 282, 1659–1664. [Google Scholar]
- Tomita, K; Tamiya, G; Ando, S; Ohsumi, K; Chiyo, T; Mizutani, A; Kitamura, N; Toda, K; Kaneko, T; Horie, Y; et al. Tumor necrosis factor alpha signaling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice. Gut 2006, 55, 415–424. [Google Scholar]
- Serviddio, G; Bellanti, F; Tamborra, R; Rollo, T; Capitanio, N; Romano, AD; Sastre, J; Vendemiale, G; Altomare, E. Uncoupling protein-2 (UCP2) induces mitochondrial proton leak and increases susceptibility of non-alcoholic steatohepatitis (NASH) liver to ischaemia-reperfusion injury. Gut 2008, 57, 957–965. [Google Scholar]
- Liu, Y; Jiang, H; He, LY; Huang, WJ; He, XY; Xing, FQ. Abnormal expression of uncoupling protein-2 correlates with CYP11A1 expression in polycystic ovary syndrome. Reprod. Fertil. Dev 2011, 4, 520–526. [Google Scholar]
- Richard, D; Rivest, R; Huang, Q; Bouillaud, F; Sanchis, D; Champigny, O; Ricquier, D. Distribution of the uncoupling protein 2 mRNA in the mouse brain. J. Comp. Neurol 1998, 397, 549–560. [Google Scholar]
- Rolfe, DFS; Hulbert, AJ; Brand, MD. Characteristics of mitochondrial proton leak and control of oxidative phosphorylation in the major oxygen-consuming tissues of the rat. Biochim. Biophys. Acta 1994, 1118, 405–416. [Google Scholar]
- Echtay, KS; Winkler, E; Klingenberg, M. Coenzyme Q is an obligatory cofactor for uncoupling protein function. Nature 2000, 408, 609–613. [Google Scholar]
- Horvath, TL; Diano, S; Leranth, C; Garcia-Segura, LM; Cowley, MA; Shanabrough, M; Elsworth, JD; Sotonyi, P; Roth, RH; Dietrich, EH; et al. Coenzyme Q induces nigral mitochondrial uncoupling and prevents dopamine cell loss in a primate model of Parkinson’s disease. Endocrinology 2003, 144, 2757–2760. [Google Scholar]
- Beal, MF; Matthews, RT; Tieleman, A; Shults, CW. Coenzyme Q10 attenuates the 1-methyl-4-phenyl-1,2,3, tetrahydropyridine (MPTP) induced loss of striatal dopamine and dopaminergic axons in aged mice. Brain Res 1998, 783, 109–114. [Google Scholar]
- Shults, CW; Oakes, D; Kieburtz, K; Beal, MF; Haas, R; Plumb, S; Juncos, JL; Nutt, J; Shoulson, I; Carter, J; et al. Effects of coenzyme Q10 in early Parkinson disease: Evidence of slowing of the functional decline. Arch. Neurol 2002, 59, 1541–1550. [Google Scholar]
- Dauer, W; Przedborski, S. Parkinson’s disease: Mechanisms and models. Neuron 2003, 39, 889–909. [Google Scholar]
- Andrews, ZB; Horvath, B; Barnstable, CJ; Elsworth, J; Yang, L; Beal, MF; Roth, RH; Matthews, RT; Horvath, TL. Uncoupling protein-2 is critical for nigral dopamine cell survival in a mouse model of Parkinson’s disease. J. Neurosci 2005, 25, 184–191. [Google Scholar]
- de la Monte, SM; Wands, JR. Molecular indices of oxidative stress and mitochondrial dysfunction occur early and often progress with severity of Alzheimer’s disease. J. Alzheimers Dis 2006, 9, 167–181. [Google Scholar]
- Blanc, J; Alves-Guerra, MC; Esposito, B; Rousset, S; Gourdy, P; Ricquier, D; Tedgui, A; Miroux, B; Mallat, Z. Protective role of uncoupling protein 2 in atherosclerosis. Circulation 2003, 107, 388–390. [Google Scholar]
- Samudio, I; Fiegl, M; Andreeff, M. Mitochondrial uncoupling and the warburg effect: Molecular basis for the reprogramming of cancer cell metabolism. Cancer Res 2009, 69, 2163–2166. [Google Scholar]
- Horimoto, M; Resnick, MB; Konkin, TA; Routhier, J; Wands, JR; Baffy, G. Expression of uncoupling protein-2 in human colon cancer. Clin. Cancer Res 2004, 10, 6203–6207. [Google Scholar]
- Kuai, XY; Ji, ZY; Zhang, HJ. Mitochondrial uncoupling protein 2 expression in colon cancer and its clinical significance. World J. Gastroenterol 2010, 16, 5773–5778. [Google Scholar]
- Bai, Y; Onuma, H; Bai, X; Medvedev, AV; Misukonis, M; Weinberg, JB; Cao, W; Robidoux, J; Floering, LM; Daniel, KW; et al. Persistent nuclear factor-kappa B activation in Ucp2-/- mice leads to enhanced nitric oxide and inflammatory cytokine production. J. Biol. Chem 2005, 280, 19062–19069. [Google Scholar]
- Derdak, Z; Fulop, P; Sabo, E; Tavares, R; Berthiaume, E; Resnick, M; Paragh, G; Wands, J; Baffy, G. Enhanced colon tumour induction in uncoupling protein-2 deficient mice is associated with NF-κB activation and oxidative stress. Carcinogenesis 2006, 27, 956–961. [Google Scholar]
- Sayeed, A; Meng, Z; Luciani, G; Chen, L-C; Bennington, JL; Dairkee, SH. Negative regulation of UCP2 by TGFβ signaling characterizes low and intermediate-grade primary breast cancer. Cell Death Dis 2010, 1. [Google Scholar] [CrossRef]
- Won, KY; Kim, GY; Kim, YW; Lim, S-J; Song, JY. Uncoupling Protein 2 (UCP2) and p53 expression in invasive ductal carcinoma of breast. Korean J. Pathol 2010, 44, 565–570. [Google Scholar]
- Wang, F; Fu, X; Chen, X; Chen, X; Zhao, Y. Mitochondrial uncoupling inhibits p53 mitochondrial translocation in TPA-challenged skin epidermal JB6 cells. PLoS One 2010, 5. [Google Scholar] [CrossRef]
- Harper, ME; Antoniou, A; Villalobos-menuey, E; Russo, A; Trauger, R; Vendemelio, M; George, A; Bartholomew, R; Carlo, D; Shaikh, A; et al. Characterization of a novel metabolic strategy used by drug-resistant tumor cells. FASEB J 2002, 16, 1550–1557. [Google Scholar]
- Nègre-Salvayre, A; Hirtz, C; Carrera, G; Cazenave, R; Troly, M; Salvayre, R; Pénicaud, L; Casteilla, L. A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation. FASEB J 1997, 11, 809–815. [Google Scholar]
- Kowaltowski, AJ; Costa, AD; Vercesi, AE. Activation of the potato plant uncoupling mitochondrial protein inhibits reactive oxygen species generation by the respiratory chain. FEBS Lett 1998, 425, 213–216. [Google Scholar]
- Kowaltowski, AJ; de Souza-Pinto, NC; Castilho, RF; Vercesi, AE. Mitochondria and reactive oxygen species. Free Radic. Biol. Med 2009, 47, 333–343. [Google Scholar]
- Derdak, Z; Mark, NM; Beldi, G; Robson, SC; Wands, JR. The mitochondrial uncoupling protein-2 promotes chemoresistance in cancer cells. Cancer Res 2008, 68, 2813–2819. [Google Scholar]
- Green, K; Brand, MD; Murphy, MP. Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes. Diabetes 2004, 53, S110–S118. [Google Scholar]
- Samec, S; Seydoux, J; Dulloo, AG. Post-starvation gene expression of skeletal muscle uncoupling protein 2 and uncoupling protein 3 in response to dietary fat levels and fatty acid composition: a link with insulin resistance. Diabetes 1999, 48, 436–441. [Google Scholar]
- Rodríguez, VM; Portillo, MP; Picó, C; Macarulla, MT; Palou, A. Olive oil feeding up-regulates uncoupling protein genes in rat brown adipose tissue and skeletal muscle. Am. J. Clin. Nutr 2002, 75, 213–220. [Google Scholar]
- Murray, AJ; Panagia, M; Hauton, D; Gibbons, GF; Clarke, K. Plasma free fatty acids and peroxisome proliferator-activated receptor alpha in the control of myocardial uncoupling protein levels. Diabetes 2005, 54, 3496–3502. [Google Scholar]
- Levine, JJ. p53, the cellular gatekeeper for growth and division. Cell 1997, 88, 323–331. [Google Scholar]
- Moll, UM; Zaikam, A. Nuclear and mitochondrial apoptotic pathways of p53. FEBS Lett 2001, 493, 65–69. [Google Scholar]
- Mihara, M; Erster, S; Zaika, A; Petrenko, O; Chittenden, T; Pancoska, P; Moll, UM. p53 has a direct apoptogenic role at the mitochondria. Mol. Cell 2003, 11, 577–590. [Google Scholar]
- Lukas, J; Niu, N; Press, MF. p53 mutations and expression in breast carcinoma in situ. Am. J. Pathol 2000, 156, 183–191. [Google Scholar]
- Zhao, Y; Chaiswing, L; Velez, JM; Batinic-Haberle, I; Colburn, NH; Oberley, TD; St Clair, DK. p53 translocation to mitochondria precedes its nuclear translocation and targets mitochondrial oxidative defense protein-manganese superoxide dismutase. Cancer Res 2005, 65, 3745–3750. [Google Scholar]
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Robbins, D.; Zhao, Y. New Aspects of Mitochondrial Uncoupling Proteins (UCPs) and Their Roles in Tumorigenesis. Int. J. Mol. Sci. 2011, 12, 5285-5293. https://doi.org/10.3390/ijms12085285
Robbins D, Zhao Y. New Aspects of Mitochondrial Uncoupling Proteins (UCPs) and Their Roles in Tumorigenesis. International Journal of Molecular Sciences. 2011; 12(8):5285-5293. https://doi.org/10.3390/ijms12085285
Chicago/Turabian StyleRobbins, Delira, and Yunfeng Zhao. 2011. "New Aspects of Mitochondrial Uncoupling Proteins (UCPs) and Their Roles in Tumorigenesis" International Journal of Molecular Sciences 12, no. 8: 5285-5293. https://doi.org/10.3390/ijms12085285